Extrachromosomal oncogene amplifications in cancer

This is a hybrid event - with the speaker attending in-person and viewable on Teams.

Extrachromosomal DNA (ecDNA) has been recognized as one of the most frequent causes of oncogene amplification in cancer. Its association with worse patient outcomes suggests that it may directly contribute to malignant cell phenotypes. This has been linked to increased oncogene dosage because both oncogenes and associated enhancers can occupy ecDNA. New data challenge the view that only oncogene dosage is affected by ecDNA, and raises the possibility that ecDNA could disrupt genome-wide gene expression. Recent investigations suggest that ecDNA localizes to specialized nuclear bodies (hubs) in which they can act in trans as ectopic enhancers for genes on other ecDNA or chromosomes. Moreover, ecDNA can reintegrate into the genome, possibly further disrupting the gene regulatory landscape in tumor cells. I will discuss the emerging properties of ecDNA and highlight promising avenues to exploit this new knowledge for the development of ecDNA-directed therapies for cancer.